title: Telomeric expression sites are highly conserved in Trypanosoma brucei.
abstract: Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom. chf@sanger.ac.uk
authors.forename: Christiane
authors.initials: C
authors.lastname: Hertz-Fowler
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Figueiredo
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quail
authors.forename: Marion
authors.initials: M
authors.lastname: Becker
authors.forename: Andrew
authors.initials: A
authors.lastname: Jackson
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bason
authors.forename: Karen
authors.initials: K
authors.lastname: Brooks
authors.forename: Carol
authors.initials: C
authors.lastname: Churcher
authors.forename: Samah
authors.initials: S
authors.lastname: Fahkro
authors.forename: Ian
authors.initials: I
authors.lastname: Goodhead
authors.forename: Paul
authors.initials: P
authors.lastname: Heath
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kartvelishvili
authors.forename: Karen
authors.initials: K
authors.lastname: Mungall
authors.forename: David
authors.initials: D
authors.lastname: Harris
authors.forename: Heidi
authors.initials: H
authors.lastname: Hauser
authors.forename: Mandy
authors.initials: M
authors.lastname: Sanders
authors.forename: David
authors.initials: D
authors.lastname: Saunders
authors.forename: Kathy
authors.initials: K
authors.lastname: Seeger
authors.forename: Sarah
authors.initials: S
authors.lastname: Sharp
authors.forename: Jesse E
authors.initials: JE
authors.lastname: Taylor
authors.forename: Danielle
authors.initials: D
authors.lastname: Walker
authors.forename: Brian
authors.initials: B
authors.lastname: White
authors.forename: Rosanna
authors.initials: R
authors.lastname: Young
authors.forename: George A M
authors.initials: GA
authors.lastname: Cross
authors.forename: Gloria
authors.initials: G
authors.lastname: Rudenko
authors.forename: J David
authors.initials: JD
authors.lastname: Barry
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Louis
authors.forename: Matthew
authors.initials: M
authors.lastname: Berriman
mesh_terms: D000818:Animals; D000940:Antigenic Variation / Q000235:genetics; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006790:Host-Parasite Interactions / Q000235:genetics; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D016324:Sequence Tagged Sites; D016615:Telomere / Q000235:genetics*; D024363:Transcription Initiation Site / Q000502:physiology*; D014346:Trypanosoma brucei brucei / Q000235:genetics* / Q000502:physiology